Download Research News

RESEARCH Ne w s
The Human Microbiome Project: fungi on human
skin
Surely every mycologist, aware of
the universe of spores and mycelium
surrounding our bodies and engulfing every
living thing, has wondered what is really
hiding in the nooks and crannies of our
bodies. The considerable attention paid
to the human microbiome in the popular
press over the past year, emphasizing that
we are composed more of bacterial cells
than human cells, that our bacterial profiles
may define our individuality and influence
our health as much as our own genes, must
have left the average mycologist wondering,
“What about the human Mycobiome?” The
latest on-line issue of Nature includes an
article that begins to address this question.
Keisha Findley et al. (2013), of the US
National Institutes of Health, studied the
skin mycobiota of ten healthy Americans,
six men and four women. The subjects
were prohibited from using antibacterial or
antifungal soaps for seven days and strictly
forbidden from showering for 24 hours
beforehand before they had skin scraped
off. The researchers sampled fourteen
parts of these healthy bodies (see figure),
including moderately embarrassing regions
such as armpits, nostrils and the inguinal
crease, and subjected the resulting DNA
to 18S cloning to identify fungal genera,
ITS pyrosequencing to identify species, and
culturing on standard medical mycology
media supplemented with olive oil to
enhance recovery of the dandruff yeasts,
Malassezia spp.
They enumerated about 80 fungal
genera, including the potentially medically
significant Candida, Chrysosporium,
Cryptococcus and otherwise unnamed
dermatophytes assigned to the
Arthrodermataceae. Common saprobic
genera such as Aspergillus, Cladosporium,
Epicoccum, Leptosphaerulina, Penicillium,
Phoma, and Rhodotorula were also
frequently detected or isolated. In common
with bacterial microbiomes reported in
other studies, the mycobiomes differed
remarkably among the people sampled,
making statistical comparisons difficult.
It is tempting to speculate on how these
differences come about. In general, feet
yielded the greatest fungal diversity, the
bottom of the heel, the toenails, the webs
between the toes. One can perhaps look at
the mycobiomes of these feet and identify
the study participants who throw off their
shoes and run through meadows, or wallow
in mud, or judging by the Saccharomyces
populations of some, stomp on wine grapes.
The authors, of course, are more serious, and
consider the past use of antifungal drugs by
their subjects, noting that their sampling
sites are those most frequently associated
with fungal infections.
The big winner in all of this is
Malassezia, the genus of lipophilic
basidiomycetes that apparently coats
our bodies with an invisible yeasty slime,
especially those parts not encased in shoes
and socks. The authors detected three
species, M. globosa, M. restricta, and M.
sympodialis, in great profusion on hands,
backs, arms and in ears, and a few apparently
undescribed species besides. Most
mycologists know about these fungi and
Human skin fungal diversity. Figure courtesy of Darryl Leja and Julia Fekecs (National Human Genome Institute, NIH).
(16) ima fUNGUS
genomes, also enable mating of Malassezia?
It would probably be best not to speculate
about this too much in grant proposals, but
nevertheless, perhaps mycologists shaking
hands at conferences now can take hidden
pleasure at the idea that they are facilitating
the continuing genomic dance of these little
cells that call our bodies home.
Findley K, Oh J, Yang J, Conian S, Deming C, et
al. (2013) Topographic diversity of fungal and
bacterial communities in human skin. Nature
doi:10.1038/nature12171f (online 22 May
2013).
Keith A. Seifert
([email protected])
Selecting the “right” genes for phylogenetic
reconstruction
It is now the normal practice in preparing
phylogenetic trees of fungal lineages to
use sequences of several different genes,
but testing whether the selected genes
are the most appropriate is necessarily
somewhat subjective. This is especially so as
incongruent trees can be produced. As more
complete fungal genomes become available,
the possibility of testing the efficacy of
particular gene sequences is becoming a
reality. In the case of the ascomycetous
yeasts, 23 whole genome sequences are now
available, across six genera. Salichos & Rokas
(2013) have investigated these to examine
phylogenomic practices where there is
incongruence from conflicting gene trees.
These researchers, from Vanderbilt
University (Nashville, TN) analysed
a staggering 1 070 orthologous genes
from across these genomes. They found
that concatenation, the compilation and
analysis of numerous genes as a single
data set, resolved the species phylogeny,
20 internodes having 100 % bootstrap
support, identical to trees recovered from
Bayesian and one type of maximumlikelihood analysis tested. However, the
tree recovered disagreed with each of the
single gene trees. An extended majority-rule
consensus (eMRC) phylogeny of the 1 070
separate gene trees gave a tree with a similar
topology, but about half of the internodes
were only weakly supported. The position
of Candida glabrata was particularly
anomalous, appearing as a sister to
Saccharomyces castellii and other species of
the latter genus – even though only 214 of
the 1 070 gene trees favoured that topology.
A novel measure to take incongruence
into account is proposed, that of “internode
certainty” based on the frequency of that
node as opposed to the most conflicting
alternatives in the same set of trees. This
measure was found to be more informative
than that of gene-support frequency (GSF).
The problem of incongruence was greatest
deepest in the phylogeny, and the authors
conclude that inferences in ancient times are
dependent on the selection of markers with
strong phylogenetic signals. They consider
that a fundamental change in current
practices is required: (1) bootstrap support
should not be used for concatenation
analyses of large data sets; (2) the signal
in individual genes and trees derived from
them should be carefully examined; and
(3) internodes that are poorly supported
should be identified explicitly. Attention
needs to be focussed on the development of
new phylogenomic approaches and markers
RESEARCH NEW S
their involvement in dandruff, but really,
what is going on here? Could it be that we
are controlled by these yeasts, that our social
customs such as hugging and kissing evolved
as mechanisms for exchanging populations
of Malassezia? Could those aspects of our
behaviour that have evolved to promote
genetic exchange among our own personal
for the resolution of ancient branches in
the genealogy of Life. This paper merits
careful scrutiny by all mycologists, and other
phylogeneticists, exploring early divergences.
Salichos L, Rokas A (2013) Inferring ancient
divergences requires genes with strong
phylogenetic signals. Nature 497: 327–331.
Candida albicans budding cell, CBS562 (scanning
electron micrograph).
Haploid Candida albicans strains and their
significance
The diverse mechanisms of reproduction
and reproductive strategies that evolved in
fungi have fascinated not only mycologists
but geneticists for generations as more and
more intriguing devices come to light. In
view of the intense attention that Candida
albicans has received in recent years from
fungal biologists, medical mycologists,
and genomics specialists, one might have
thought there was nothing basic yet to be
volume 4 · no. 1
uncovered. Not so; there was one secret
of success that had remained hidden until
now. The yeast cells from clinical cases
are invariably diploid (Gow 2013), but
now Hickman et al. (2013) have found
that a halploid state serendipitously in the
course of in vitro experiments on the loss
of heterozygosity. They then used flow
cytometry, which enables the amount of
DNA in individual cells to be measured, to
screen isolates from a wide range of in vivo
and in vitro sources. They found another
haploid that had been growing in the halo
of the antifungal drug flucanizole, and
occurred in vivo at the rate of 1–3 haploid
cells in every 100 000 cells – no wonder
they had not been picked up before!
This finding is of especial significance
as it means that some genes that might
otherwise have arisen by mutation, and
(17)
RESEARCH Ne w s
not been expressed in a diploid because
of suppression by genes on the other
chromosome set, may be. When a haploid
cell forms, that can continue to divide
mitotically, and then either form a diploid
by mating with a haploid with a different
chromosome set to form a regular diploid,
Candida albicans clusters of conidia, CBS562.
(18) or with an identical haploid to form an
auto-diploid. In the auto-diploid, genes
not normally expressed can potentially be
perpetuated and spread in a population. In
the particular auto-diploids studied, growth
was less rapid than in normal diploid strains,
Candida albicans producing thick-walled clamydospores, CBS562.
which may partly have caused it to be
overlooked by previous workers.
This newly discovered strategy for
generating diversity in this most versatile
yeast can now be added to those of
tetraploid formation with subsequent
chromosome loss back to diploid, the
production of aneuploids by duplicating
some chromosomes, and the mating of
compatible diploids (Gow 2013). I wonder
what other secrets this fungus still hides . .
...
Gow NAR (2013) Multiple mating strategies.
Nature 494: 45–46.
Hickman MA, Zeng G, Forche A, Hirakawa MP,
Abbey D, Harrison BD, Wang Y-M, Su C-H,
Bennett RJ, Wang Y, Berman J (2013) The
‘obligate diploid’ Candida albicans forms
mating-competent halploids. Nature 494:
55–59.
ima fUNGUS